Preview

Medical Immunology (Russia)

Advanced search

Clinical significance of class II HLA genes (DRB1, DQA1 and DQB1) in tick-born encephalitis

https://doi.org/10.15789/1563-0625-SCO-3016

Abstract

Tick-borne encephalitis is a natural endemic disease which is widely spread in Russia. The purpose of the study was to determine clinical significance of HLA class II genes in tick-borne encephalitis. We observed 75 patients with tick-borne encephalitis admitted to the Kirov Hospital of Infectious Diseases and district hospitals over 2020-2023. Molecular typing of the HLA genes DRB1, DQA1 and DQB1 was carried out using PCR technique, with a set of commercial sequence-specific primers (“DNA-Technology”, Russian Federation). The febrile form of tick-borne encephalitis was noted in 41.3% of patients; focal, in 34.7%; meningeal, in 16.0%, inapparent, in 8% of cases. The comparison group for HLA DRB1 locus included 1528 practically healthy individuals from the same population. Comparison group for HLA DQA1 and DQB1 genes comprised 133 persons. The study has revealed a number of HLA class II genes, which are found significantly more often in TBE patients, rather than in control group (DRB1*1 (χ2 = 12.2; pc < 0.01), DRB1*4 (χ2 = 6 .4; pc < 0.05), DRB1*7 (χ2 = 11.7; pc < 0.01), DRB1*8 (χ2 = 4.6; pc < 0.05), DRB1*13 (χ2 = 7.7; pc < 0.01), DRB1*15 (χ2 = 9.3; pc < 0.01), DRB1*16 (χ2 = 14.3; pc < 0.01), DQA1*0102 (χ2 = 7.6; pc < 0.01), DQB1*0401-2 (χ2 = 3.9; pc < 0.05), DQB1*0502-4 (χ2 = 8.1; pc < 0.01). Among HLA class II haplotypes, the susceptibility to the development of tick-borne encephalitis was determined by the combinations DRB1*08-DQA1*0401-DQB1*401/402 (χ2 = 5.7; pc < 0.05), DRB1*09-DQA1*0301- DQB1*303 (χ2 = 5.7; pc < 0.05) and DRB1*16-DQA1*0102-DQB1*502 (χ2 = 7.4; pc < 0.01). Carriage of the DRB1*15 gene was most risky for development of febrile form of tick-borne encephalitis, (χ2 = 7.8; pc < 0.01; RR = 3.1). Occurrence of three-locus haplotypes DRB1*09-DQA1*0301-DQB1*303 (χ2 = 8.8; pc < 0.01), and DRB1*16-DQA1*0102-DQB1*502 (χ2 = 5.0; pc < 0.05) was associated with increased risk of developing a febrile form of TE by 14.5 and 10.9 times, respectively. In patients with meningeal form of EC, compared with healthy individuals, the gene variants DRB1*08 (χ2 = 12.9; pc < 0.01), DQA1*401 (χ2 = 3.9; pc < 0.05), DQB1*401/402 (χ2 = 9.1; pc < 0.01) were significantly more common. The presence of a threelocus haplotype DRB1*16-DQA1*0102-DQB1*502 (χ2 = 10.9; pc < 0.01) increases the risk of developing a focal TBE by 17.7 times. Thus, tick-borne encephalitis is associated with certain HLA class II alleles, which may be used as a prognostic criterion for development of different clinical forms of tick-borne encephalitis, or tick-borne encephalitis in general.

About the Authors

O. N. Lyubeznova
Kirov State Medical University
Russian Federation

Lyubeznova O.N., PhD (Medicine), Associate Professor, Department of Infectious Diseases 

112 K. Marx St., Kirov 610912


Competing Interests:

 

 



A. L. Bondarenko
Kirov State Medical University
Russian Federation

Bondarenko A.L., PhD, MD (Medicine), Professor, Head, Department of Infectious Diseases 

112 K. Marx St., Kirov 610912


Competing Interests:

 

 



References

1. Aliseychik M.P., Andreeva T.V., Rogaev E.I. Immunogenetic Factors of Neurodegenerative Diseases: The Role of HLA Class II. Biokhimiya = Biochemistry, 2018, Vol. 83, Iss. 9, pp. 1104-1116. (In Russ.)

2. Bondarenko A.L. HLA and diseases. Kirov, 1999. 194 p.

3. Bondarenko A.L., Tikhomolova E.G., Zykova I.V., Kontyakova E.L., Zyanchurina G.M. Prognostic significance of immunoregulatory Th1 and Th2 cytokines in tick-borne encephalitis. Infektsionnyye bolezni = Infectious Diseases, 2011, no. 1, pp. 28-32. (In Russ.)

4. Gergert V.Ya., Pospelov A.L., Stavitskaya N.V., Kordicheva S.Yu., Soroko-Novitskaya A.N., Pospelov L.E. Comparison of the distribution of HLADRB1 locus genes in healthy children and adolescents with tuberculosis in different populations. Tuberkulez i bolezni legkikh = Tuberculosis and Lung Diseases, 2010, Vol. 87, no. 9, pp. 29-32. (In Russ.)

5. Zima A.P., Ryazantseva N.V., Novitsky V.V., Zhukova O.B., Zhukova N.G., Lepechin A.V., Radzivil T.T. Imbalance in IL-2 and IL-4 production and reception during prolonged viral antigenemia in tick-born encephalitis Meditsinskaya immunologiya = Medical Immunology (Russia), 2008, Vol. 10, no. 4-5, pp. 389-396. (In Russ.) doi: 10.15789/1563-0625-2008-4-5-389-396.

6. Idrisova Zh.R., Petrukhin A.S., Uchaikin V.F., Dekonenko E.P. Clinical significance of determining the DRB1 gene of the major histocompatibility complex in viral encephalitis. Pediatriya. Zhurnal im. G.N. Speranskogo = Pediatrics. Journal named after G.N. Speransky, 2000, Vol. 79, no. 4, p. 4. (In Russ.)

7. Kolyasnikova N.M., Ishmukhametov A.A., Akimkin V.G. The current state of the problem of tick-borne encephalitis in Russia and the world. Epidemiologiya i Vaktsinoprofilaktika = Epidemiology and Vaccinal Prevention, 2023, Vol. 22, no. 1, pp. 104-123. (In Russ.)

8. Krylova N.V. History and prospects for studying the immunogenetic aspects of the pathogenesis of tick-borne encephalitis. Dalnevostochnyy zhurnal infektsionnoy patologii = Far Eastern Journal of Infectious Pathology, 2007, no. 11, pp. 46-51. (In Russ.)

9. Loginova M.A., Trofimova N.P., Paramonov I.V. Genetic features of the population living in the Kirov region. Vestnik sluzhby krovi Rossii = Bulletin of the Russian Blood Service, 2012, no. 1, pp. 24-28. (In Russ.)

10. Lyubeznova O.N., Bondarenko A.L., Utenkova E.O., Kontyakova E.L. Pathomorphosis of tick-borne encephalitis in the Kirov region. Infektsionnye bolezni = Infectious Diseases, 2015, Vol. 13, no. 1, pp. 46-52. (In Russ.)

11. Maksimov O.D., Zaitseva G.A., Butina E.V., Zagoskina T.P., Fedorovskaya N.A., Kopaneva T.G. Distribution of HLA markers in chronic lymphocytic leukemia. Gematologiya i transfuziologiya = Hematology and Transfusiology. 2003, Vol. 43, no. 1, pp. 19-22. (In Russ.)

12. Ratnikova L.I., Ter-Baghdasaryan L.V., Mironov I.L. Modern ideas about the pathogenesis of tick-borne encephalitis. Epidemiologiya i infektsionnye bolezni = Epidemiology and Infectious Diseases, 2002, no. 5, pp. 41-46. (In Russ.)

13. Solovyova A.S. Genetic control of the immune response. Byulleten fiziologii i patologii dykhaniya = Bulletin of Physiology and Pathology of Respiration, 2014, Vol. 51, pp. 130-136. (In Russ.)

14. Smolnikova M.V., Konenkov V.I. Clinical immunogenetics of human diseases. Meditsinskaya immunologiya = Medical Immunology (Russia), 2001, Vol. 3, no. 3, pp. 379-389. (In Russ.)

15. Suslova E.V., Khlebnikova N.V., Suetina I.G., Illek Y.Yu. Immunogenetic parameters for atopic dermatitis in children of different ages. Vyatskiy meditsinskiy vestnik = Vyatka Medical Bulletin, 2020, no. 4 (68), pp. 8-11. (In Russ.)

16. Troshina E.A., Yukina M.Yu., Nuralieva N.F., Mokrysheva N.G. The role of HLA genes: from autoimmune diseases to COVID-19. Problemy endokrinologii = Problems of Endocrinology, 2020, Vol. 66, no. 4, pp. 9-15. (In Russ.)

17. Chernitsyna L.O., Prokofiev V.F., Konenkov V.I., Jerusalemsky A.P. Immunogenetic methods in the prognosis of the clinical course of tick-borne encephalitis. Zhurnal nevropatologii i psikhiatrii im. S.S. Korsakova = Journal of Neuropathology and Psychiatry named after. S.S. Korsakov, 1990, Vol. 90, no. 11, pp. 38-43. (In Russ.)

18. Anzurez A., Naka I., Miki S., Nakayama-Hosoya K., Isshiki M., Watanabe Y., Nakamura-Hoshi M., Seki S., Matsumura T., Takano T., Onodera T., Adachi Y., Moriyama S., Terahara K., Tachikawa N., Yoshimura Y., Sasaki H., Horiuchi H., Miyata N., Miyazaki K., Koga M., Ikeuchi K., Nagai H., Saito M., Adachi E., Yotsuyanagi H., Kutsuna S., Kawashima A., Miyazato Y., Kinoshita N., Kouno C., Tanaka K., Takahashi Y., Suzuki T., Matano T., Ohashi J., Kawana-Tachikawa A. Association of HLA-DRB1*09:01 with severe COVID-19. HLA, 2021, Vol. 98, no. 1, pp. 37-42.

19. Atrashevskaya A.V., Ignatyev G.M., Fredeking T.M. Chages in immune parameters and their correction in human cases of tick-borne encephalitis. Clin. Exp. Immunol., 2003, Vo.131, no. 1, pp. 148-154.

20. Kovalchuka L., Eglite J., Zalite M. The frequency of HLA-DR alleles in patients with tick-borne disease from Latvia. Res. J. Infect. Dis., 2014, Vol. 2, 4. doi: 10.7243/2052-5958-2-4.

21. Kovalchuka L., Eglite J., Lucenko I., Zalite M. Associations of HLA DR molecules with Lyme borreliosis in Latvian patients. BMC Res. Notes, 2012, no. 5, 438. doi: 10.1186/1756-0500-5-438.

22. Liu J., Wei H., Liu J., Peng L., Li G., Li M., Yang L., Jiang Y., Peng F. Analysis of the association of HLA subtypes with cryptococcal meningitis in HIV-negative immunocompetent patients. Future Microbiol., 2022, Vol. 17, pp. 1231-1240.

23. Moutsianas L., Jostins L., Beecham A.H., Dilthey A.T., Xifara D.K., Ban M., Shah T.S., Patsopoulos N.A., Alfredsson L., Anderson C.A., Attfield K.E., Baranzini S.E., Barrett J., Binder T.M., Booth D., Buck D., Celius E.G., Cotsapas C., D’Alfonso S., Dendrou C.A., Donnelly P., Dubois B., Fontaine B., Fugger L., Goris A., Gourraud P. A., Graetz C., Hemmer B., Hillert J., International IBD Genetics Consortium (IIBDGC), Kockum I., Leslie S., Lill C.M., Martinelli-Boneschi F., Oksenberg J.R., Olsson T., Oturai A., Saarela J., Søndergaard H.B., Spurkland A., Taylor B., Winkelmann J., Zipp F., Haines J.L., Pericak-Vance M.A., Spencer C.C., Stewart G., Hafler D.A., Ivinson A.J., Harbo H.F., Hauser S.L., De Jager P.L., Compston A., McCauley J.L., Sawcer S., McVean G. Class II HLA interactions modulate genetic risk for multiple sclerosis Nat. Genet., 2015, Vol. 47, no. 10, pp. 1107-1113.

24. Nguyen A., David J.K., Maden S.K. Human leukocyte antigen susceptibility map for SARS-CoV-2. J. Virol., 2020, Vol. 94, no. 13, e00510-20. doi: 10.1128/JVI.00510-20.

25. Smith K.J., Pyrdol J., Gauthier L., Wiley D.C., Wucherpfennig K.W. Crystal Structure of HLA-DR2 (DRA*0101, DRB1*1501) Complexed with a Peptide from Human Myelin Basic Protein. J. Exp. Med., 1998, Vol. 188, no. 8, pp. 1511-1520.

26. Steer A.C., Falk B., Drouin E.E., Baxter-Lowe L.A., Hammer J., Nepom G.T. Binding of outer surface protein A and human lymphocyte function-associated antigen 1 peptides to HLA-DR molecules associated with antibiotic treatment-resistant Lyme arthritis. Arthritis Rheum., 2003, Vol. 48, no. 2, pp. 534-540.

27. Werner J., Rivera N., Grunewald J., Eklund A., Iseda T., Darlington P., Kullberg S. HLA-DRB1 alleles associate with hypercalcemia in sarcoidosis. Respir. Med., 2021, Vol. 187, 106537. doi: 10.1016/j.rmed.2021.106537.


Supplementary files

Review

For citations:


Lyubeznova O.N., Bondarenko A.L. Clinical significance of class II HLA genes (DRB1, DQA1 and DQB1) in tick-born encephalitis. Medical Immunology (Russia). 2025;27(2):317-328. (In Russ.) https://doi.org/10.15789/1563-0625-SCO-3016

Views: 152


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)